| dc.description.abstract | Severe infections are common causes of hospitalization, morbidity, and mortality worldwide. It is important to improve our understanding of why some individuals are more susceptible to severe infections than others. Therefore, this thesis aims to identify genetic variants and modifiable risk factors that potentially affects the risk of severe infections.
In the first paper, a genome-wide association study (GWASs) was performed to investigate the association between genetic variants and susceptibility to lower respiratory tract infection. We used genetic data from participants in UK Biobank, the Trøndelag Health Study (HUNT), and FinnGen. We found that a genetic region on chromosome 15 was strongly associated with the risk of lower respiratory tract infection. Furthermore, it was found that this effect was only present among smokers. Using so-called “Mendelian randomization” (MR), we found that genetically predicted smoking, high body mass index, and high systolic blood pressure were associated with an increased risk of genetically predicted lower respiratory tract infection.
In the second paper, MR analyses were conducted to investigate the association between genetically predicted iron biomarkers levels and genetically predicted risk of sepsis and severe COVID-19. For sepsis and COVID-19, we used data from UK Biobank and the COVID-19 Host Genetics Initiative (HGI), respectively. We found that individuals with higher iron biomarkers levels had an increased risk of developing sepsis. In addition, we found a tendency that higher serum iron levels were associated with a higher risk of developing severe COVID-19.
In the third paper, MR analyses were conducted to explore the relationship between genetically predicted blood levels of micronutrients and the risk of developing gastrointestinal infection, pneumonia, and urinary tract infection. For the infectious disease outcomes, we used data from UK Biobank and FinnGen. We found that high blood levels of copper were associated with a reduced risk of developing gastrointestinal infections. Furthermore, we observed no clear association between the other included micronutrients and infections.
Finally, in the fourth work, we conducted a GWAS to examine the association between genetic variants and susceptibility to upper urinary tract infection. Genetic data from UK Biobank, HUNT, and the Michigan Genomics Initiative (MGI) was used. We found that genetic variants in the human leucocyte antigen (HLA) region on chromosome 6 and near the TSN gene on chromosome 2 were associated with the susceptibility of upper urinary tract infection; the latter was only linked to the risk of upper urinary tract infection in women and not in men. The MR analyses showed that smoking increased the risk of developing upper urinary tract infection.
This thesis identified several genetic variants associated with the susceptibility to lower respiratory tract infection and upper urinary tract infection. Several modifiable risk factors were found to influence the risk of severe infections. | en_US |
